1. Field of the Invention
The present invention relates generally to drug concentration sensors. More specifically, the present invention relates to a method and device to form a sensor using isolated cardiomyocytes. The sensor of the present invention is formed from endogenous tissue using an ablation catheter to ablate a cone- or dome-shaped region of tissue in the heart to form an electrically isolated tissue section of cardiomyocytes. An electrode is fixed to the region of isolated tissue and is used to detect the electrophysiological activity of this electrically independent cluster of cells. These cells combined with the electrode and a detection circuitry will form a cell based sensor to monitor the effects of the anti-arrhythmic drugs in the circulation.
2. Background of the Invention
It can be appreciated that drug concentration sensors have been in use for years. Typically, drug concentration sensors are comprised of point of care measurement systems where the concentration of drugs in the circulation can be measured from blood drawn from patients.
The main problem with conventional drug concentration sensors is that they do not provide continuous data unless the sensor is implanted. Sensors created from cells native to the body would not suffer from such problems. Edelberg et al. [Am J Physiol Heart Circ Physiol 280: H2006–H2010, 2001] demonstrated the feasibility of using cardiac cells to sense drug concentrations by implanting donor cardiomyocytes into a non-cardiac site in a recipient animal and monitoring them electrophysiologically while administering pharmaceutical agents. The present invention takes the concept one step further by turning it into a catheter and lead based procedure and eliminates the need for a donor tissue, although donor cells or tissue can be used with the present invention.
The present invention also provides a solution to the problem of patient compliance in taking prescribed medications. Most anti-arrhythmic drugs are prescribed to patients with chronic conditions such as atrial fibrillation and ventricular tachycardia. However, a general problem is patient compliance in taking their medical prescription. If the implantable device could monitor the effect of the drug on the cardiac rhythm, this information could be used for closed loop drug delivery. Closed loop delivery of the drug with integration of the sensors of the present invention also provides improved avenues for more effective use and delivery of drug.
A further improvement of the present invention is in providing a demand based delivery system based on functional measurements from the isolated cardiomyocytes. Most medications are taken at routine times during the day. Because schedule-based delivery only estimates the actual need, often the effective concentration of the drug are less than optimal. A closed loop system utilizing the isolated tissue sensor provides a means to monitor the body's direct requirements for the drug, and then delivers the proper dose on a demand basis.
Another problem with conventional drug concentration sensors is that artificial sensors utilizing synthetic enzymes require periodic replacement of the enzyme that they use, limiting the useful life of the sensor. Sensors using the natural cells of the body would not require the periodic maintenance and the resupply of conventional sensors, making them very suitable for implantable applications.
While sensors described in the prior art may be suitable for the particular purpose that they address, they generally are not as suitable for long-term implantation. Most implantable sensors suffer from problems related to stability and sensor encapsulation. Cells native to the body would not suffer from such problems.
In these respects, the method and device to form a sensor using a cardiomyocyte according to the present invention substantially depart from the conventional concepts and designs of the prior art, and in so doing provide an apparatus primarily developed for such a purpose. In order to create a sensor of the present invention, typically a catheter is advanced into the tissue of interest, cardiac in the preferred embodiment, and is then used to ablate a cone- or a dome-shaped region in the tissue to form an electrically isolated section of tissue. An electrode is later fixed to the region encompassed by the dome-shaped area of tissue and used to detect the electrophysiological activity of this electrically independent cluster of cells. These cells combined with the electrode and a detection circuitry can be used to form a cell-based sensor to monitor the effects of the anti-arrhythmic drugs in the circulation without the chronotopic influence existing on the remainder of the myocardial cells.